Micro-Fluidic Temperature Driven Valve

Abstract

Subject of the present invention is a micro-fluidic device for the use in an apparatus for analyzing a liquid sample by nucleic acid amplification, an apparatus for analyzing a liquid sample by nucleic acid amplification, a method for analyzing a liquid sample and a method for amplifying nucleic acids in a liquid.

1 . A micro-fluidic device for the use in an apparatus for analyzing a liquid sample by nucleic acid amplification, comprising:
 a reaction chamber having an inlet channel suitable for filling said reaction chamber with said liquid sample;   said inlet channel further containing at least one micro-fluidic valve comprising a dead end branch, said dead end branch having no outlet and containing a gas and being dimensioned to at least contain the amount of gas sufficient to seal said inlet channel when said gas expands from said dead end branch into said inlet channel to form a diffusion barrier capable of reversibly sealing said inlet channel when said dead end branch is heated; and   an outlet suitable for the discharge of fluid from said reaction chamber, said outlet being closable after the reaction chamber is filled with said liquid sample.   
     
     
         2 . The micro-fluidic device according to  claim 1 , wherein said dead end branch is substantially perpendicular to said inlet channel. 
     
     
         3 . The micro-fluidic device according to  claim 1 , wherein the inner wall of said inlet channel at least at the junction between said dead end branch and said inlet channel is covered with a hydrophobic coating. 
     
     
         4 . The micro-fluidic device according to  claim 1 , further comprising a plurality of reaction chambers, each reaction chamber having an inlet channel and an outlet, wherein each inlet channel further contains at least one micro-fluidic valve comprising a dead end branch, said dead end branch having no outlet and containing a gas and being dimensioned to at least contain the amount of gas sufficient to seal said inlet channel when said gas expands from said dead end branch into said inlet channel to form a diffusion barrier capable of reversibly sealing said inlet channel when said dead end branch is heated. 
     
     
         5 . The micro-fluidic device according to  claim 4 , wherein each inlet channel is at one end linked to one reaction chamber and on the other end linked to a main channel, said main channel being effective to transfer to each of said plurality of reaction chambers at least a portion of said liquid sample. 
     
     
         6 . The micro-fluidic device according to  claim 1 , wherein said inlet channel contains a micro-fluidic valve comprising at least two dead end branches and wherein the openings of said dead end branches into the inlet channel are positioned adjacent to another or substantially opposite to another. 
     
     
         7 . The micro-fluidic device according to  claim 1 , wherein the outlet is an outlet channel and comprises a geometric valve and/or at least one dead end branch and/or a hydrophobic coating. 
     
     
         8 . An apparatus for analyzing a liquid sample by nucleic acid amplification, comprising:
 a micro fluidic device according to  claim 1 ,   a device for monitoring the nucleic acid amplification reaction, and   a heating device at least covering said at least one dead end branch of said micro-fluidic device.   
     
     
         9 . The apparatus according to  claim 8 , wherein said heating device further covers said reaction chamber of said micro-fluidic device. 
     
     
         10 . The apparatus according to  claim 8 , further comprising a heat control device. 
     
     
         11 . The apparatus according to  claim 8 , wherein said heating device is capable of performing thermal cycling. 
     
     
         12 . A method for analyzing a liquid sample by nucleic acid amplification, comprising:
 providing a liquid sample in the reaction chamber of a micro-fluidic device according to  claim 1  via the inlet channel of said device,   applying heat to at least the dead end branch of said device by a heating device, whereby the gas within the dead end branch expands from said dead end branch into said inlet channel to form a diffusion barrier and to thereby reversibly seal the inlet channel of said device,   amplifying nucleic acids in said liquid sample, and   monitoring the amplification reaction.   
     
     
         13 . A method for amplifying nucleic acids in a liquid sample, comprising:
 providing a liquid sample in the reaction chamber of a micro-fluidic device according to  claim 1  via the inlet channel of said device,   applying heat to at least the dead end branch of said device by a heating device, whereby the gas within the dead end branch expands from said dead end branch into said inlet channel to form a diffusion barrier and to thereby reversibly seal the inlet channel of said device, and   amplifying nucleic acids in said liquid sample.   
     
     
         14 . The method according to  claim 12  or  claim 13 , further comprising closing the inlet and/or the outlet channel after the reaction chamber is filled with said liquid sample and before said step of applying heat to the dead-end branch of said device. 
     
     
         15 . The method according to  claim 12  or  claim 13 , wherein nucleic acids are amplified using polymerase chain reaction, ligase chain reaction, nucleic acid sequence-based amplification, rolling circle amplification, strand-displacement amplification, isothermal amplification, touchdown polymerase chain reaction or transcription-mediated amplification.